The role of mast cells in humans is the same as in animals. In addition, animals contain counterparts to human .varies.-1-antichymotrypsin, .varies.-1-antitrypsin and other serine protease inhibitors. In fact, it has been shown that human .varies.-1-antitrypsin will bind with animal mast cell mediators.
It has been reported by Froll et al in Carcinogenesis, Vol. 2. Mechanism of Tumor Promotion and Carcinogenesis, New York, Raven; (1978) p. 301-312, that cancer cells secrete elevated amounts of proteolytic enzymes, including serine proteases, at the earliest steps in carcinogenesis, and that intracellular levels of .varies.-1-antitrypsin (.varies.1-PI), as well as extracellular milieu of tumors are increase. However, the proteolytic activities of the aggressive cancer-associated proteases are not efficiently inhibited.
It is also known that a cancer cell alone endowed with a latent gene DNA code for a peptide secreted by cancer cells which is introduced by a virus as a protooncogene remains suppressed until activated by a cancer proliferation promoting agent which also triggers the synthesis of cancer-associated serine proteases. Viruses such as hepatitis virus and herpes virus are the most common viruses which promote cancer cell activity.
Alpha 1-antichymotrypsin is a plasma protease inhibitor synthesized in the liver. It is a single glycopeptide chain of approximately 68,000 daltons and belongs to a class of serine protease inhibitors with an apparent affinity toward chymotrypsinlike enzymes.
Alpha 2-macroglobulin is a glycoprotein containing 8-11% carbohydrate which can be isolated from plasma by gel filtration chromatography.
Alpha 1-proteinase inhibitor (alpha 1-antitrypsin) is a glycoprotein having a molecular weight of 53,000 determined by sedimentation equilibrium centrifugation. The glycoprotein consists of a single polypeptide chain to which several oligosaccharide units are covalently bonded. Human alpha 1-proteinase inhibitor has a role in controlling tissue destruction by endogenous serine proteinases. A genetic deficiency of alpha 1-proteinase inhibitor, which accounts for 90% of the trypsin inhibitory capacity in blood plasma, has been shown to be associated with the premature development of pulmonary emphysema. The degradation of elastin associated with emphysema probably results from a local imbalance of elastolytic enzymes and the naturally occurring tissue and plasma proteinase inhibitors. Alpha-1-proteinase inhibitor inhibits human pancreatic and leukocyte elastases. See Pannell et al, Biochemistry. 13, 5339 (1974); Johnson et al, Biochem. Biophys. Res. Commun., 72 33 (1976); Del Mar et al, Biochem. Biophys. Res. Commun., 88, 346 (1979); and Heimburger et al, Proc, Int. Res. Conf. Proteinase Inhibitors. 1st, 1-21 (1970).
It is understood that the term "serine protease inhibitors" as used herein refers to the inhibitors derived from a particular species and inhibits the proteases of the same species. However, human serine protease inhibitors may be used in veterinary products but not visa versa.